In performing simple movements humans scale parameters of motor output. For example, movements are sometimes made quickly and sometimes slowly. During complex movements, multiple single movements must be sequenced together in the spatial and temporal domains to produce purposeful motor behavior such as in playing the piano. The basal ganglia-thalamo-cortical system is thought to play an important role in scaling parameters of motor output and generating movement sequences. Over the past several decades models of basal ganglia circuitry have been developed in animals that describe how neurotransmitters change the inhibitory and excitatory properties of specific basal ganglia nuclei. However, the task-dependent connectivity of each basal ganglia nucleus with cortical networks in humans remains unknown. The long-range goal of our research program is to develop a task-dependent model in humans for how the basal ganglia interacts with cortical regions to scale motor output and generate movement sequences. We propose a research plan that will precisely manipulate well structured motor tasks. We will carefully measure motor behavior and image each basal ganglia nucleus in addition to associated brain structures in humans using functional magnetic resonance imaging (fMRI) at 3 Tesla. Previous literature and our preliminary work presented in section C lead us to test the hypothesis that each basal ganglia nucleus controls specific processes associated with scaling and sequencing of motor output. The specific aims are: 1) To determine how each basal ganglia nucleus scales in activation with the force amplitude; 2) To determine how each basal ganglia nucleus scales in activation with the rate of force development; 3) To determine which of the basal ganglia nuclei control unpredictable and predictable force sequences; and 4) To determine how each nucleus of the basal ganglia interacts with cortical networks during externally-selected and internally-selected force sequences. The innovation of this proposal is that we will delineate the task-dependent function of small basal ganglia targets in humans. As such, the proposal will have direct application to understanding the motor deficits of millions of Americans who suffer from basal ganglia dysfunction such as Parkinson's disease, stroke, dystonia, and Huntingdon's disease. [unreadable] [unreadable]